运用网络药理学和实验验证探讨补肝健膝方治疗膝骨关节炎的作用机制  

To Explore the Mechanism of Bugan Jianxi Prescription(补肝健膝方)in the Treatment of Knee Osteoarthritis by Network Pharmacology and Experimental Verification

作　　者：许辉[1] 张信成[1] 曾朝晖 尹晨东 匡建军[1,2] XU Hui;ZHANG Xincheng;ZENG Zhaohui;YIN Chendong;KUANG Jianjun(Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine,Changsha Hunan 410006,China;Hunan Traditional Chinese Medicine College,Zhuzhou Hunan 412012,China)

机构地区：[1]湖南省中医药研究院附属医院,湖南长沙410006 [2]湖南中医药高等专科学校,湖南株洲412012

出　　处：《中医药导报》2023年第3期36-42,48,共8页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：长沙市科技创新平台项目(kh2201063);湖南省科学技术厅临床创新引导项目(2020SK51002);长沙市科技局项目(kq2004046)。

摘　　要：目的:运用网络药理学与实验验证方法研究补肝健膝方治疗膝骨关节炎的潜在作用机制。方法:通过多个数据库筛选补肝健膝方的活性化合物及其治疗膝骨关节炎的相关靶点;检索GeneCards数据库、OMIM数据库、TTD数据库、CTD数据库获取膝骨关节炎的靶点;采用交集法进而获得补肝健膝方与膝骨关节炎的相关靶点;利用Cytoscape软件构建活性成分-交集靶点调控网络,并对交集靶点进行网络拓扑分析;利用Metascape数据库对交集靶点进行GO和KEGG富集分析;制备膝骨关节炎新西兰兔模型,观察补肝健膝方干预效果,检测核心靶点在关节液中的表达。结果:补肝健膝方中筛选活性成分靶点593个,膝骨关节炎靶点824个,药物-疾病共同靶点138个,关键靶点涉及TNF-α、IL1B、MMP9、TP53、VEGFA、ALB、AKT1、EGF等。GO功能富集分析GO条目6 076个,主要涉及细胞迁移的正调控、防御反应、对脂多糖的反应、炎症反应、细胞黏附的调节等;KEGG通路富集分析得到251条信号通路,包括AGE-RAGE信号通路、JAK-Stat信号通路、NF-κB信号通路、TGF-β信号通路等。动物实验结果显示,与空白组比较,模型组新西兰兔关节液中TNF-α、IL-1β含量显著升高(P<0.05);与模型组比较,独活寄生汤组和补肝健膝方组TNF-α、IL-1β表达水平均有不同程度下降(P<0.05)。结论:补肝健膝方可能通过多靶点、多通路调节细胞生存周期、抗氧化、抗炎等发挥治疗膝骨关节炎的作用。Objective:To study the potential mechanism of Bugan Jianxi Prescription in the treatment of knee osteoarthritis by network pharmacology and experimental verification.Methods:The active compounds of Bugan Jianxi Prescription and their related targets for the treatment of knee osteoarthritis were screened through multiple databases.The targets of knee osteoarthritis were obtained by searching GeneCards database,OMIM database,TTD database and CTD database.The intersection method was used to obtain the related targets of Bugan Jianxi Prescription and knee osteoarthritis.Cytoscape software was used to construct the active ingredient-intersection target regulatory network,and the network topology analysis of the intersection target was carried out.GO and KEGG enrichment analysis was performed on the intersection targets using the Metascape database.The New Zealand rabbit model of knee osteoarthritis was prepared to observe the intervention effect of Bugan Jianxi Prescription and detect the expression of core targets in synovial fluid.Results:A total of 593 targets of active ingredients,824 targets of knee osteoarthritis and 138 common targets of drug-disease were screened in Bugan Jianxi Prescription. The key targets involved TNF-α, IL1B, MMP9, TP53, VEGFA, ALB, AKT1, EGF and so on. GO functional enrichment analysis of 6 076 GO items, mainly related to the positive regulation of cell migration, response to wounding, response to lipopolysaccharide, inflammatory response, regulation of cell adhesion, etc. KEGG pathway enrichment analysis obtained 251 signaling pathways, including AGE-RAGE signaling pathway, JAK-STAT signaling pathway, NF-κB signaling pathway, TGF-β signaling pathway, etc. The results of animal experiments showed that compared with the blank group, the contents of TNF-α and IL-1β in the synovial fluid of New Zealand rabbits in the model group were significantly increased (P<0.05). Compared with the model group, the expression levels of TNF-α and IL-1β in Duhuo Jisheng Decoction group and Bugan Jian

关 键 词：膝骨关节炎 补肝健膝方 网络药理学 分子对接 作用机制 

分 类 号：R285.5[医药卫生—中药学]